Isentress Going Strong After Three Years in Treatment Starters

July 21, 2009

By Tim Horn

Long-term data from a Phase II clinical trial show that Merck’s integrase inhibitor Isentress (raltegravir) works just as well as mainstay therapy efavirenz (found in Sustiva and Atripla) in HIV-positive individuals starting treatment for the first time. These encouraging results were reported Monday, July 20, by Eduardo Gotuzzo, MD, of the Hospital Nacional Cayetano Heredia in Lima, Peru, and his colleagues at the Fifth International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention in Cape Town.

Isentress was originally approved for treatment-experienced people living with HIV. On July 8, however, the U.S. Food and Drug Administration allowed its use in patients beginning HIV treatment for the first time. The original 48-week data from Protocol 004, one of the studies used to support Isentress’s approval for treatment-naïve individuals, were reported at the last IAS conference, held two years ago in Sydney.

Gotuzzo’s group enrolled 198 HIV-positive people starting treatment for the first time to receive either Isentress at one of the six doses—explored in the first 48 weeks of the study, with all patients in the Isentress group then switched to 400 mg twice daily—or 600 mg Sustiva once daily. All patients in the study also received Viread (tenofovir) and Epivir (lamivudine).

Upon entering the study, the average viral load was 55,000 copies in the Isentress group and 67,000 in the Sustiva group. After 144 weeks of therapy, 78 percent of patients in the Isentress group maintained viral loads below 50 copies/mL. In the Sustiva group, about 76 percent of patients maintained viral loads below 50 copies/mL. This difference was not statistically significant, meaning that the slight variation could have been due to chance.

CD4 counts, averaging 305 cells in the Isentress group and 280 cells in the Sustiva group at the start of the study, increased in all patients after 144 weeks or treatment. Among patients in the Isentress group, CD4 counts increased by 253 cells. In the Sustiva group, CD4 counts increased by 233 cells. As with the viral load results, this minute difference was not statistically significant.

Five patients (3 percent) in the Isentress groups and one patient (3 percent) in the Sustiva group experienced virologic failure while in the study, defined as either a viral load that failed to go undetectable by week 24 or a viral load rebound after an initial undetectable result. Mutations believed to be associated with resistance to integrase inhibitors—N155H, V151I, D232D/N and G163R/G in HIV’s integrase gene—were documented in two of the five Isentress-treated patients.

Gotuzzo reported that side effects were generally similar between Isentress and Sustiva. Overall, 54 percent of those in the Isentress group experienced a drug-related adverse event, compared with 76 percent of those in the Sustiva group. And while 2.6 percent of patients had a serious drug-related adverse effect in the Sustiva group, no such serious problems were documented in the Isentress group.

Diarrhea, nausea, dizziness and headache were documented in both groups of patients. Neuropsychiatric adverse events—such as abnormal dreams, depression and suicidal thoughts—were less common in patients in the Isentress groups compared with those in the Sustiva group.

As for lipid levels, total cholesterol increased by 6.8 mg/dL in the Isentress group, compared with a 33.5 mg/dL increase in the Sustiva group. LDL “bad” cholesterol decreased by 1.9 mg/dL in the Isentress group, compared with an increase of 10.5 mg/dL in the Sustiva group. The difference between the Isentress and Sustiva groups with respect to triglyceride changes was not statistically significant.

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